Alpha-1 Antitrypsin Deficiency Study – Phase II

A Preliminary Study of the Efficacy and Safety of Carbamazepine in Severe Liver Disease Due to Alpha-1-Antitrypsin Deficiency

Protocol Description

Girl and boy teens standing back to backThis research study, being carried out at Children’s Hospital of Pittsburgh of UPMC and Presbyterian Hospital of UPMC, is designed to determine whether carbamazepine (CBZ), a drug which has been used safely for many years for seizures and depression, can reduce the severity of liver disease that occurs in some people with the genetic disorder known as alpha-1 antitrypsin (AT) deficiency, or ATD. In this disorder a genetic mutation results in the formation of an abnormal protein that accumulates in liver cells. This accumulation is toxic to the liver cells and therefore leads to gradual scarring (fibrosis) and ultimately failure of the liver to function properly (cirrhosis). Researchers from Children’s Hospital have shown that CBZ stimulates a process that removes abnormal proteins from cells in animal models of ATD. CBZ, also known by the trade name Tegretol-XR, is currently FDA approved for use by children in the treatment of seizures, depression and facial pain due to nerve inflammation.

Study Level: Phase II

Eligibility Criteria

Subject to certain exclusion criteria, this study is accepting patients of both genders, ages 14 through 80, with liver disease due to alpha-1 antitrypsin deficiency.
Males: 14 years through 80 years
Females: 14 years through 80 years


Participants will be randomly assigned to groups that will either take CBZ or a placebo, prepared in identical appearing capsules. Two thirds of the subjects will take CBZ and one-third will take placebo. Dosages will be increased weekly for the first five weeks, and monitoring of the drug level in the blood will be done throughout the study to reduce side effects. Liver biopsies and measurement of liver pressure will be done at the beginning of the study and at week 52, after which the study medication will be stopped.
Visits: 7
Duration: Approximately 1 year

Status: Open for Enrollment

Source(s) of Support

National Institutes of Health

Primary Investigator

Robert H. Squires, MD

Contact Information

For information or to enroll, please contact:
Adam Kufen, RN, BS, CCRC